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タイトル CAR T cell therapy: Challenges and potential strategies for solid tumor
講演者 Dr. Supannikar Tawinwung
所属 Chulalongkorn University
開催日 2019-05-14 17:00
終了日
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この度、招聘教員としてタイChulalongkorn大学よりおこしのSupannikar Tawinwung先生に、下記の要領で研究セミナーを行って頂きます。

日時: 2019年5月14日(火) 17:00〜18:00
場所: 薬学部本館第2講堂
演者: Dr. Supannikar Tawinwung (Chulalongkorn University)

演題: CAR T cell therapy: Challenges and potential strategies for solid tumor 

The adoptive transfer of T cells engineered to express tumor specific chimeric antigen receptors (CARs) has emerged as an effective tool for the treatment of hematologic malignancies. Chimeric antigen receptor (CARs) are recombinant receptors composed of antigen-binding domain and T-cell-activating domain. CAR is encoded by a single gene consisting of single chain variable fragments (scFVs) as antigen binding domain, transmembrane domain, and signaling domain, which generally included signaling transduction domain of T cell receptor (TCR) and costimulatory receptor. CAR-T targeting CD19 in CD19+ B cell malignancies has provided outstanding clinical responses, and in 2017, the US Food and Drug Administration has approved the first CAR-T targeting CD19 for B cell acute lymphoblastic leukemia.  However, the success of CAR T cells in solid tumor has been limited. This is partly due to the complexity of solid tumor that acts as a barrier for T cell trafficking as well as the immunosuppressive cytokines and immunosuppressive cells such as regulatory T cells and myeloid derived suppressor cells present in the tumor microenvironment. For example, in breast cancer microenvironment, there are upregulated immunosuppressive cytokines, including interleukin -4, interleukin -10 and TGF-b, which suppress tumor specific T cells function. In order to protect our CAR T cells from the suppressive tumor milieu, we have designed an inverted cytokine receptor, where the IL-4 receptor exodomain is linked with the endodomain of IL-7 receptor (4/7ICR). This inverted cytokine receptor transforms the suppressive signal of IL-4 into the stimulatory effect of IL-7 receptor. We have shown that co-expression of the 4/7ICR with CAR rescued CAR T cell function from the inhibitory effects of IL-4 in vitro. Besides, these 4/7ICR expressing CAR T cell expanded and provided durable anti-tumor activity in vivo.  

 

連絡先:
薬学研究院 医薬細胞生化学分野
藤田雅俊